Systems and methods for performing optical spectroscopy using a self-calibrating fiber optic probe
Systems and methods for performing optical spectroscopy using a self-calibrating fiber optic probe are disclosed. One self-calibrating fiber optic probe includes a sensing channel for transmitting illumination light to a specimen and for collecting spectral data of the specimen. The spectral data includes the illumination light diffusely reflected from the specimen at one or more wavelengths. The self-calibrating fiber optic probe may also include a calibration channel for transmitting calibration light. The calibration light and the illumination light are generated simultaneously from a common light source. The calibration channel collects calibration spectral data associated with the calibration light contemporaneously with the collection of the spectral data of the specimen.
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This application claims the benefit of U.S. Provisional Patent Application Ser. No. 61/047,818, filed Apr. 25, 2008, the disclosure of which is incorporated herein by reference in its entirety.
GOVERNMENT INTERESTThis presently disclosed subject matter was made with U.S. Government support under Grant No. 1R01CA100559 awarded by NIH. Thus, the U.S. Government has certain rights in the presently disclosed subject matter.
TECHNICAL FIELDThe subject matter disclosed herein relates to optical spectroscopy and calibration techniques pertaining to fiber optic measurement instruments. More particularly, the subject matter disclosed herein relates to systems and methods for performing optical spectroscopy using a self-calibrating fiber optic probe.
BACKGROUNDDiffuse reflectance spectroscopy (DRS) is sensitive to the absorption and scattering properties of biological molecules in tissue and therefore can be used as a noninvasive in vivo tool to obtain quantitative information about the physiological and morphological properties (e.g., biomarkers) of human tissue. Thus, DRS can be utilized specifically as a diagnostic tool to detect various diseases that alter human tissue properties. Potential clinical applications of DRS include precancer detection and cancer diagnostics, intraoperative tumor margin assessment, and monitoring of tumor response to chemotherapy. Fiber optic probes are commonly used to deliver illumination light to, and collect diffusely reflected light from, a tissue specimen for DRS measurements. However, in order for DRS to be utilized in a clinic, frequent calibration is typically required to correct or compensate for a number of factors, such as lamp intensity fluctuations, wavelength-dependent instrument response, interdevice variations, and fiber bending losses that occur while a measurement is taken.
Calibration techniques presently used by biophotonics researchers typically rely on measurements using power meters, reflectance standards, and/or tissue phantoms (i.e., models that simulate human tissue and blood vessels). These calibration procedures are usually performed after the clinical measurements are completed. One particular DRS calibration method involves a two-step calibration procedure that utilizes the measured spectra of a spectrally flat diffuse reflectance standard (i.e., a reflective Spectralon puck) and a phantom of known optical properties in order to obtain the absolute reflectance spectra of a tissue sample. For example, a calibrated reference phantom spectrum is obtained by dividing the collected phantom spectrum with the collected puck spectrum. Similarly, a calibrated tissue spectrum is obtained by dividing a collected tissue spectrum with a second collected puck spectrum (i.e., a 2nd spectrum measurement of the same calibration puck). More specifically, calibration is performed by dividing the tissue spectra point by point by the spectra of the puck. Afterwards, a ratio of the calibrated tissue spectrum and the calibrated reference phantom spectrum is input into an inverse Monte Carlo model, which in turn extracts the optical properties of the tissue.
The aforementioned calibration of the tissue spectrum against a reference phantom is needed to put the experimental and Monte Carlo simulated data on the same scale. This is typically necessary no matter what type of calibration method is employed. However, the calibration of the tissue spectra and reference phantom spectra to the puck spectra is carried out to account for day-to-day system variations that occur between the time of the tissue measurement and the time of the reference phantom measurement.
There are a number of limitations associated with spectral data calibration methods currently utilized. Notably, these calibration methods fail to correct or compensate for real-time system fluctuations, such as variations in lamp intensity. For example, a given DRS illumination source typically requires at least 30 minutes of warm-up time to prevent significant light intensity fluctuations. However, the 30 minute warm-up period can pose considerable unwanted delays in a clinical setting, such as an operating room. Remarkably, light intensity of a light source can change as much as 25% during the warm-up period and even 3% afterwards. These variations in intensity are significant considering a 5% change in light intensity can introduce approximately 20% error in the extraction of optical properties from a tissue sample.
Another problem that arises in optical spectroscopy is the error caused by bending the optical fibers of the probe. Sharp bending frequently occurs in clinical applications, such as endoscopy, where the fiber optic probe is manually handled. For example, bending the detection arm (all 200 μm fibers) of the probe to a diameter of 3 cm (three turns) causes 6% light intensity attenuation, while bending the probe even further to a diameter of 2 cm can cause 11% attenuation in light intensity. As mentioned above, a 5% change in intensity can result in approximately 20% error in extracted optical properties from a tissue specimen.
Traditional calibration techniques typically rely on measurements from tissue phantoms and/or a diffuse reflectance standard that are usually performed after the clinical measurements are completed. Although these traditional calibration methods are successful in correcting instrument throughputs and remove day-to-day system drifts, none of the calibration methods are able to correct for real-time lamp fluctuations and fiber-bending loss while the specimen measurement is made. Similarly, all traditional calibration methods require at least 30 minutes for warming up the light source and a time-consuming calibration test procedure that is separate from the collection of the tissue sample spectra. As indicated previously, the reduction of unnecessary delays or procedures is extremely desirable in a clinical setting.
Thus, there remains a need for an improved system and method for performing optical spectroscopy using a self-calibrating fiber optical probe.
SUMMARYThe subject matter described herein includes systems and methods for performing optical spectroscopy using a self-calibrating fiber optical probe. According to one aspect, the self-calibrating fiber optic probe includes a sensing channel for transmitting illumination light to a specimen and for collecting spectral data of the specimen, wherein the spectral data includes the illumination light diffusely reflected from the specimen at one or more wavelengths. The self-calibrating fiber optic probe may also include a calibration channel for transmitting calibration light, wherein the calibration light and the illumination light are generated simultaneously from a common light source, and collecting calibration spectral data associated with the calibration light contemporaneously with the collection of the spectral data of the specimen.
Preferred embodiments of the subject matter described herein will now be described with reference to the accompanying drawings, of which:
The subject matter described herein includes systems and methods for performing optical spectroscopy using a self-calibrating fiber optic probe. The present subject matter includes a fast, robust, and systematic calibration approach that can be used for correcting spectral data of a specimen obtained in real-time and with different instruments and probes. More specifically, the present subject matter includes a fiber optic probe with self-calibration capability configured for performing diffuse reflectance spectroscopy (DRS). The probe includes a built-in calibration channel that can be used to record the light source spectrum and instrument-fiber responses contemporaneously with tissue spectra measurements. Combined with a one-time single-reference phantom measurement, the self-calibrating fiber optic probe can provide instrument-independent optical properties.
The illumination fiber leg 114 of probe 102 may include illumination source fiber 122, for illuminating the sample, and calibration source fiber 124, for internal calibration. In one embodiment, each of illumination source fiber 122 and calibration source fiber 124 are 600 μm diameter fibers. In another embodiment, a plurality of 200 μm diameter illumination source fibers (instead of a single 600 μm diameter illumination source fiber) and/or at least one 200 μm diameter calibration source fiber (instead of a single 600 μm diameter calibration source fiber) may be used for increased instrument flexibility. The collection fiber leg 116 may include eight detection fibers 126 that are coupled to spectrograph 108 and are configured to collect the diffusely reflected light from sample 118 at one or more wavelengths. In one embodiment, detection fibers 126 are 200 μm diameter fibers. Collection fiber leg 116 may also include at least one calibration return fiber 128 for collecting the calibration light (which, like the illumination light, is generated by light source 104) reflected by a reflective element 302 (see
In one embodiment, the collected diffuse reflectance and beams of calibration light carried by the calibration return and detection fibers are diffracted and projected onto different areas of CCD camera 110 and recorded by processing unit 112. In one embodiment, a two-dimensional CCD camera 110 operates in a multi-track manner that enables it to obtain both the specimen spectrum and calibration spectrum (i.e., spectral data from light carried in calibration return fiber 124) simultaneously. There may be an equivalent of one, but not limited to one collection fiber spacing between the self-calibration and sensing areas on the CCD with no measurable cross talk. In one embodiment, a miniature spectrometer may be used for each channel (i.e., the sensing channel and calibration channel). Practically speaking, the at least one calibration return fiber may be coupled to a first spectrometer, while the at least one detection fiber may be coupled to a second spectrometer. Similarly, the at least one calibration return fiber and the at least one detection fiber may each instead be respectively coupled to a separate and dedicated spectrograph and/or photodetector.
Once the spectral data is received by the processing unit 112 from the spectrograph 108 and CCD camera 110, processing unit 112 may ultimately execute an algorithm to interpret the spectral data and extract the optical properties of sample 118 from the probe measurements. In one embodiment, the algorithm may include a Monte Carlo algorithm that is executed by processing unit 112. Similarly, the Monte Carlo algorithm may also include an inverse Monte Carlo reflectance algorithm or an inverse Monte Carlo fluorescence algorithm. An exemplary Monte Carlo algorithm suitable for use with the subject matter described herein is found in international patent application number PCT/US2007/006624 to Palmer and Ramanujam and U.S. patent application publication 2006/0247532 to Ramanujam et al. An exemplary scaling method for expediting calculations performed in the Monte Carlo algorithm is described in U.S. provisional patent application Ser. No. 60/903,177, filed Feb. 23, 2007. In an alternative embodiment, a diffusion algorithm or an inverse diffusion algorithm may be used instead of a Monte Carlo algorithm.
In addition to having two physical optical fiber groupings, fiber optic probe 102 may also comprise two separate “channels”, each of which is distributed between both the illumination fiber leg 114 and collection fiber leg 116. Namely, a self-calibrating fiber optic probe may include a sensing channel and a built-in calibration channel. In one embodiment, the sensing channel includes at least one illumination source fiber (e.g., illumination source fiber 122) that traverses illumination fiber leg 114 and at least one detection fiber (e.g., detection fibers 126) that traverses collection fiber leg 116. Similarly, the calibration channel may comprise at least one calibration source fiber (e.g., calibration source fiber 124) that traverses illumination fiber leg 114 and at least one calibration return fiber (e.g., calibration return fibers 128) that traverses collection fiber leg 116. In one embodiment, the self-calibrating probe can be used to concurrently measure the spectral data of light source 104 and the spectral data of sample 118. Notably, this configuration is advantageous in a clinical setting because the configuration accounts for the real-time light source intensity fluctuations and fiber bending loss (i.e., light intensity fluctuations caused by bending the instrument). For example, the bending effect on illumination source fiber 122 is assumed to be the same as that of calibration source fiber 124. Also, light source warm-up time and separate calibration measurements are also unnecessary with a self-calibrating fiber optic probe. In addition, the sensing channel and the calibration channel may also refer to a first CCD channel on CCD camera 110 that includes all the detection fibers binned together and a second CCD channel on CCD camera 110 that includes all the calibration return fibers binned together as depicted in cross-sectional view 123 in
Fiber optic probe 102 may also include rigid elements 224-228 (e.g., t-tubes and ferrules) that provide stability and/or interfacing capability for fiber optic probe 102. Rigid probe tip 223 may include a plurality of fibers arranged in a configuration as shown in cross-section 120 (see
After the light is emitted by the illumination source fiber 122 on sample 118, at least one detection fiber 126 captures the reflected light (i.e., spectral data of sample) which may ultimately be provided to spectrograph 108 via the fiber array shown in cross-sectional view 123 (see
In one embodiment, calibration source fiber 124 and calibration return fiber 128 may comprise the same exact fiber (i.e., a source/return calibration fiber). For example, a single source-return calibration fiber may originate from light source 104, enter housing section 224, and bent or looped back in such a manner that the calibration source/return fiber exits housing section 224. That is, the calibration source-return fiber is bent within housing section 224 in the fiber optic probe such that the calibration source fiber functions as the calibration return fiber (since a mirror or other reflective element is not used). The calibration fiber would then be configured to interface with spectrograph 108 via collection arm 116. Notably, reflective element 302 would not be utilized in this particular embodiment.
At the same time the illumination light from light source 104 traverses illumination source fiber 122, light (i.e., calibration light) is traversing calibration source fiber 124. More specifically, the calibration light and the illumination light are generated by light source 104 at the same time and contemporaneously traverse illumination fiber leg 114. While the light traversing illumination source fiber 122 proceeds to sample 118, the light in calibration source fiber 124 is directed to reflection element 302. The reflected light from calibration source fiber 124 is then directed to and received by calibration return fiber 128, which in turn carries the reflected light to spectrograph 108. In one embodiment, spectrograph 108 receives the reflected light in calibration return fiber 128 contemporaneously with the diffusely reflected light carried by detection fibers 126.
In block 404, the collected spectral data is processed to derive calibrated specimen spectral data. In one embodiment, the specimen spectral data (i.e., diffusely reflected light) is divided by the calibration spectral data (i.e., reflected light from calibration return fiber 128) on a spectrum point by point basis to obtain calibrated specimen spectral data. This calibration of the specimen spectral data is performed to account for real-time intensity fluctuations of the light source and fiber bending effects, as well as wavelength dependent system response in system 100.
In one embodiment, the calibration spectral data may have a correlation factor applied before being processed with the specimen spectral data. Because the calibration channel may have wavelength responses that differ from the wavelength responses exhibited in the sensing channel, the wavelength response in the calibration channel may require correction and/or compensation. For example, to correct the calibration channel's wavelength dependence, a spectral measurement may be taken from a reflectance standard (e.g., a Spectralon puck), which is characterized by a flat wavelength response. A correction factor may be generated for each probe by dividing the spectral data of the reflectance standard by the self-calibration spectrum (e.g., the spectral data of the light provided to spectrograph 108 by calibration return fiber 128) concurrently obtained with the spectral data of the reflectance standard. For example, the correlation factor may be the ratio, Fcorr(λ)=[RPuck(λ)]/[RSC(λ)], which serves as correction of the calibration channel in terms of wavelength response. Notably, this correlation factor need only be determined once and can be used for the lifetime of a given self-calibrating fiber optic probe.
In block 406, the self-calibration spectral data and reference spectral data are used to derive calibrated reference spectral data. In one embodiment, reference spectral data includes spectral data of a phantom (i.e., a model that simulates human tissue and blood vessels). The reference spectral data is also divided by the aforementioned self-calibration spectral data (with or without the application of the correlation factor) on a spectrum point by point basis to obtain calibrated reference spectral data. Although method 400 depicts block 406 being performed after block 404, the collection of the reference spectral data is a one time procedure for each probe and instrument combination and may instead be performed before block 404 without departing from the scope of the present subject matter.
In block 408, the calibrated spectral data is input into an algorithm. In one embodiment, both the calibrated tissue spectral data and the calibrated reference spectral data respectively obtained in block 404 and 406 are input into an inverse Monte Carlo model algorithm executed by processing unit 112.
In block 410, optical properties of the specimen are extracted. In one embodiment, once the calibrated spectral data is processed via the inverse Monte Carlo model, the processing unit 112 is configured to derive optical properties (e.g., scatterers and absorbers) of sample 118.
It will be understood that various details of the presently disclosed subject matter may be changed without departing from the scope of the presently disclosed subject matter. Furthermore, the foregoing description is for the purpose of illustration only, and not for the purpose of limitation.
Claims
1. A self-calibrating fiber optic probe comprising:
- a sensing channel for transmitting illumination light to a specimen and for collecting spectral data of the specimen, wherein the spectral data includes the illumination light diffusely reflected from the specimen at one or more wavelengths, wherein the sensing channel includes at least one illumination source fiber for transmitting the illumination light to the specimen and at least one detection fiber for collecting the illumination light diffusely reflected from the specimen; and
- a calibration channel for transmitting calibration light, wherein the calibration light and the illumination light are generated simultaneously from a common light source, and collecting calibration spectral data associated with the calibration light contemporaneously with the collection of the spectral data of the specimen, wherein the calibration channel includes at least one calibration source fiber for transmitting the calibration light and at least one calibration return fiber for receiving at least a portion of the calibration light from the at least one calibration source fiber and wherein the at least one calibration source fiber and the at least one illumination source fiber comprise separate fibers having identical numerical apertures.
2. The fiber optic probe of claim 1 wherein the at least one calibration source fiber and the at least one calibration return fiber are the same optical fiber.
3. The fiber optic probe of claim 2 wherein the at least one calibration source fiber is bent within a probe tip housing section in the fiber optic probe such that the at least one calibration source fiber functions as the at least one calibration return fiber.
4. The fiber optic probe of claim 1 wherein the at least one calibration source fiber and the at least one illumination source fiber are constructed from the same type of materials and include identical core diameters and clad diameters, and wherein the at least one detection fiber and the at least one calibration return fiber are constructed from the same type of materials and include identical numerical apertures, core diameters and clad diameters.
5. The fiber optic probe of claim 1 wherein the at least one calibration source fiber directs at least a portion of the calibration light to a reflective element to be reflected to and received by the at least one calibration return fiber.
6. The fiber optic probe of claim 5 wherein the reflective element includes at least one of a mirror, a reflective rod, and a polished metal element.
7. The fiber optic probe of claim 1 wherein the at least one calibration return fiber and the at least one detection fiber are coupled to at least one of a spectrograph, spectrometer, or photodetector.
8. The fiber optic probe of claim 1 wherein the at least one calibration return fiber is coupled to at least one of a first spectrograph, a first spectrometer, or a first photodetector, and the at least one detection fiber is coupled to at least one of a second spectrograph, a second spectrometer, or a second photodetector.
9. The fiber optic probe of claim 1 wherein the at least one calibration return fiber includes a primary calibration return fiber and a backup calibration return fiber.
10. The fiber optic probe of claim 1 wherein the specimen includes a tissue or a turbid medium.
11. The fiber optic probe of claim 1 wherein the fiber optic probe comprises at least one of a forward firing fiber optic probe or a side firing fiber optic probe.
12. The fiber optic probe of claim 1 wherein the calibration channel includes a reflective element, wherein the at least one calibration source fiber directs at least a portion of the calibration light to the reflective element to be reflected to and received by the at least one calibration return fiber, wherein the calibration channel further includes a housing for housing the at least one calibration source fiber, the at least one calibration return fiber, and the reflective element, wherein the at least one calibration source fiber terminates within the housing, and wherein the at least one illumination source fiber extends completely through the housing to interface with the specimen.
13. A system for performing self-calibrating diffuse reflectance spectroscopy, the system comprising:
- a fiber optic probe that includes: a sensing channel for transmitting illumination light to a specimen and for collecting spectral data of the specimen, wherein the spectral data includes the illumination light diffusely reflected at one or more wavelengths from the specimen, wherein the sensing channel includes at least one illumination source fiber for transmitting the illumination light to the specimen and at least one detection fiber for collecting the illumination light diffusely reflected from the specimen; and
- a calibration channel for transmitting calibration light, wherein the calibration light and the illumination light are generated simultaneously from a light source, and for collecting calibration spectral data associated with the calibration light contemporaneously with the collection of the spectral data of the specimen, wherein the calibration channel includes at least one calibration source fiber for transmitting the calibration light and at least one calibration return fiber for receiving at least a portion of the calibration light from the at least one calibration source fiber and wherein the at least one calibration source fiber and the at least one illumination source fiber comprise separate fibers having identical numerical apertures;
- a processing unit, coupled to the sensing channel and the calibration channel, for receiving the spectral data of the specimen and the calibration spectral data to generate calibrated specimen spectral data in real-time.
14. The system of claim 13 wherein the at least one calibration source fiber and the at least one calibration return fiber are the same optical fiber.
15. The system of claim 13 wherein the at least one calibration source fiber is bent within a probe tip housing section in the fiber optic probe such that the at least one calibration source fiber functions as the at least one calibration return fiber.
16. The system of claim 13 wherein the at least one calibration source fiber and the at least one illumination source fiber are constructed from the same type of materials and include identical, core diameters and clad diameters, and wherein the at least one detection fiber and the at least one calibration return fiber are constructed from the same type of materials and include identical numerical apertures, core diameters and clad diameters.
17. The system of claim 13 wherein the at least one calibration source fiber directs at least a portion of the calibration light to a reflective element to be reflected to and received by the at least one calibration return fiber.
18. The system of claim 17 wherein the reflective element includes at least one of a mirror, a reflective rod, and a polished metal element.
19. The system of claim 13 wherein the at least one calibration return fiber includes a primary calibration return fiber and a backup calibration return fiber.
20. The system of claim 13 wherein the specimen includes a tissue or a turbid medium.
21. The system of claim 13 wherein the fiber optic probe comprises at least one of a forward firing fiber optic probe or a side firing fiber optic probe.
22. The system of claim 13 wherein the light source includes at least one of a xenon lamp or a white light emitting diode (LED) source.
23. The system of claim 13, wherein the processing unit comprises a spectrometer and a computer for receiving contemporaneously the spectral data of the specimen from the at least one detection fiber and the calibration spectral data from the at least one calibration return fiber.
24. The system of claim 23 wherein the calibration spectral data represents effects of at least one of real-time light source intensity fluctuations and real-time attenuation of the calibration light caused by bending of the fiber optic probe.
25. The system of claim 24 wherein the processing unit applies a correlation factor to the calibration spectral data to generate modified calibration spectral data.
26. The system of claim 25 wherein the correlation factor comprises a ratio between spectral data associated with a diffuse reflectance standard and the calibration spectral data that is collected concurrently.
27. The system of claim 26 wherein the processing unit processes the spectral data of the specimen and the modified calibration spectral data to produce calibrated specimen spectral data.
28. The system of claim 27 wherein the calibrated specimen spectral data is an input to a Monte Carlo algorithm or a diffusion algorithm that derives optical properties of the specimen.
29. The system of claim 28 wherein the Monte Carlo algorithm includes either an inverse Monte Carlo reflectance algorithm or an inverse Monte Carlo fluorescence algorithm.
30. The system of claim 29 wherein the diffusion algorithm includes an inverse diffusion algorithm.
31. The system of claim 13 wherein the calibration channel includes a reflective element, wherein the at least one calibration source fiber directs at least a portion of the calibration light to the reflective element to be reflected to and received by the at least one calibration return fiber, wherein the calibration channel further includes a housing for housing the at least one calibration source fiber, the at least one calibration return fiber, and the reflective element, wherein the at least one calibration source fiber terminates within the housing, and wherein the at least one illumination source fiber extends completely through the housing to interface with the specimen.
32. A method for utilizing a self-calibrating fiber optic probe comprising:
- transmitting illumination light via a sensing channel from a light source to a specimen, wherein the sensing channel includes at least one illumination source fiber for transmitting the illumination light to the specimen and at least one detection fiber for collecting the illumination light diffusely reflected from the specimen;
- transmitting calibration light via a calibration channel, wherein the calibration light and the illumination light are generated simultaneously from the light source, wherein the calibration channel includes at least one calibration source fiber for transmitting the calibration light and at least one calibration return fiber for receiving at least a portion of the calibration light from the at least one calibration source fiber and wherein the at least one calibration source fiber and the at least one illumination source fiber comprise separate fibers having identical numerical apertures;
- collecting spectral data of the specimen via the sensing channel, wherein the spectral data includes the illumination light diffusely reflected from the specimen at one or more wavelengths; and
- collecting calibration spectral data associated with the calibration light via the calibration channel contemporaneously with the collection of the spectral data of the specimen.
33. The method of claim 32 wherein the at least one calibration source fiber and the at least one calibration return fiber are the same optical fiber.
34. The method of claim 33 wherein the at least one calibration source fiber is bent within a probe tip housing section in the method such that the at least one calibration source fiber functions as the at least one calibration return fiber.
35. The method of claim 32 wherein the at least one calibration source fiber and the at least one illumination source fiber are constructed from the same type of materials and include identical, core diameters and clad diameters, and wherein the at least one detection fiber and the at least one calibration return fiber are constructed from the same type of materials and include identical numerical apertures, core diameters and clad diameters.
36. The method of claim 32 further comprising:
- directing at least a portion of the calibration light via the at least one calibration source fiber to a reflective element to be reflected to and received by the at least one calibration return fiber.
37. The method of claim 36 wherein the reflective element includes at least one of a mirror, a reflective rod, and a polished metal element.
38. The method of claim 32 wherein the at least one calibration return fiber and the at least one detection fiber are coupled to at least one of a spectrograph, spectrometer, or photodiode.
39. The method of claim 32 wherein the at least one calibration return fiber is coupled to at least one of a first spectrograph, a first spectrometer, or a first photodiode, and the at least one detector fiber is coupled to at least one of a second spectrograph, a second spectrometer, or a second photodiode.
40. The method of claim 32 wherein the at least one calibration return fiber includes a primary calibration return fiber and a backup calibration return fiber.
41. The method of claim 32 wherein the specimen includes a tissue or a turbid medium.
42. The method of claim 32 wherein the method comprises at least one of a forward firing fiber optic probe or a side firing fiber optic probe.
43. The method of claim 32 wherein the calibration channel includes a reflective element, wherein the at least one calibration source fiber directs at least a portion of the calibration light to the reflective element to be reflected to and received by the at least one calibration return fiber, wherein the calibration channel further includes a housing for housing the at least one calibration source fiber, the at least one calibration return fiber, and the reflective element, wherein the at least one calibration source fiber terminates within the housing, and wherein the at least one illumination source fiber extends completely through the housing to interface with the specimen.
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Type: Grant
Filed: Apr 27, 2009
Date of Patent: Aug 12, 2014
Patent Publication Number: 20110295541
Assignee: Duke University (Durham, NC)
Inventors: Bing Yu (Cary, NC), Nirmala Ramanujam (Chapel Hill, NC)
Primary Examiner: Gregory J Toatley
Assistant Examiner: Maurice Smith
Application Number: 12/989,591
International Classification: G01J 3/00 (20060101); G01J 3/40 (20060101); G01J 3/42 (20060101); G01J 3/28 (20060101); G01N 21/47 (20060101); G01J 3/02 (20060101); G01N 21/27 (20060101); G01N 21/49 (20060101);